Transfer of nitroimidazoles from contaminated beeswax to honey.

Nitroimidazoles are not authorised for the treatment of honey bees in the European Union. However, they can be found in honey largely because they are illegally used in apiculture for the treatment of Nosema. The aim of the study was to examine the possible transfer of nitroimidazoles (metronidazole, ronidazole, dimetridazole and ipronidazole) from contaminated beeswax to honey. The wax foundations fortified with a mixture of four nitroimidazoles at three concentration levels (1000, 10,000 and 100,000 µg kg-1) were placed in beehives to let the honeybees (Apis mellifera L.) draw out the contaminated wax foundations to honeycombs. At 1 month from the start, the frames filled with capped honey were removed from the hives for a first sampling of honey. Next, the honeycombs were further incubated for 5 months in the laboratory at 35°C and sampled monthly. In the sampled honey, the concentrations of nitroimidazoles and their main metabolites (hydroxymetronidazole, 2-hydroxymethyl-1-methyl-5-nitroimidazole, hydroxyipronidazole) were determined by LC-MS/MS and compared with those determined in the nitroimidazole-containing wax foundations. Each of the tested nitroimidazoles could migrate from beeswax to honey kept in the contaminated combs at each tested concentration level. Higher maximum concentrations of residues in honey sampled from contaminated combs at 1000, 10,000 and 100,000 µg kg-1 were observed for metronidazole (28.9, 368.5 and 2589.4 µg kg-1 respectively) and ronidazole (27.4, 232.9 and 2351.2 µg kg-1 respectively), while lower maximum concentrations were measured for dimetridazole (0.98, 8.4 and 67.7 µg kg-1) and ipronidazole (0.9, 7.9 and 35.7 µg kg-1 respectively). When we took into account that a frame completely filled with honey on both sides of the comb contained 110 g of beeswax and 2488 g of honey, and that this ratio was constant, then maximum amounts of initial metronidazole, ronidazole, dimetridazole and ipronidazole that migrated from contaminated wax foundations to honey could be calculated: 65-89%, 55-63%, 1.7-2.7% and 1.4-2.3%, respectively.

Cryptosporidium muris infection in bilbies (Macrotis lagotis).

Cryptosporidiosis is an enteric disease of animals and humans that can be fatal in immunocompromised individuals. There is no known effective treatment for cryptosporidiosis. Bilbies are threatened marsupials and are bred in captivity as part of a recovery program to re-introduce this species to the southwest of Western Australia. Cryptosporidium muris infection was detected in the faeces of bilbies at a captive breeding colony. Stress associated with a high density of bilbies in enclosures may have predisposed some of the bilbies to infection with C. muris. C. muris has been described in mice and was found in the faeces of one mouse trapped in the breeding enclosures. It is likely the bilbies acquired the infection from mice by faecal contamination of food and water. The infection cleared within 2 months from some bilbies, however others remained infected for 6 months and treatment was attempted with dimetridazole. Subsequently the parasite was no longer be detectable in the faeces.

Homeopathy versus antibiotics in metaphylaxis of infectious diseases: a clinical study in pig fattening and its significance to consumers.

CONTEXT: Due to the conditions of modern industrial pig fattening in intensive livestock farms, 24% to 69% of the animals become ill. The antibiotic metaphylaxis that is routinely administered leads to several problems in animals, human health, and the environment. OBJECTIVE: To investigate whether a homeopathic metaphylaxis is effective and potentially useful for replacing antibiotic metaphylaxis. DESIGN: Animal subjects were divided into groups of 10 per pen, 2 pens sharing 1 trough. Twenty pigs were randomly assigned within a stall and were administered either antibiotics, homeopathy, or placebo. SETTING: A typical intensive livestock farm in Northern Germany. PARTICIPANTS: 1440 piglets. INTERVENTION: Homeopathic metaphylaxis is compared with placebo, the routine low-dose antibiotic metaphylaxis, and an antibiotic metaphylaxis in therapeutic dosage. MAIN OUTCOME MEASURES: Incidence of diseases in general and of diseases of the respiratory tract. RESULTS: Homeopathic metaphylaxis is significantly effective compared with placebo and routine low-dose antibiotic metaphylaxis for incidence of disease and rate of disease of the respiratory tract among the animals studied. Only by increasing the dosage of antibiotics to a therapeutic level does antibiotic metaphylaxis surpass homeopathic metaphylaxis. CONCLUSIONS: An unacceptably high percentage of pigs in modern livestock management become ill, suffering mainly from diseases of the respiratory tract. The routine antibiotic dosage of metaphylaxis is too low to be effective. As a result, the problems of resistance and danger to human health and the environment are increasing. To confirm whether antibiotic metaphylaxis may be replaced by homeopathic metaphylaxis, this study should be repeated independently.

Pharmacokinetics and anti-trichomonal efficacy of a dimetridazole tablet and water-soluble powder in homing pigeons (Columba livia).

The anti-trichomonal efficacy and pharmacokinetics of dimetridazole were investigated in the homing pigeon (Columba livia). Dimetridazole was formulated for drinking water medication and as a prolonged-release tablet. To suppress a Trichomonas gallinae infection successfully, medicated drinking water containing dimetridazole (400 mg/L) had to be administered for at least 3 days. A two-day treatment with a dimetridazole tablet (20 mg/tablet) in fasted, as well as in fed, pigeons was shown to be ineffective. After intravenous administration of 20 mg dimetridazole, the drug plasma concentration-time profile fitted a one-compartment open model with a mean half-life of 3.9 h. The absolute bioavailability of the tablet in fasted pigeons was 83.8%. The bioavailability of the tablet administered with food was reduced by 20%. Dimetridazole was rapidly metabolised to (1-methyl-5-nitroimidazol-2-yl) methanol.

Residues of dimetridazole in eggs after treatment of laying hens.

Laying hens were dosed orally with dimetridazole (DMZ) (50 and 250 mg/kg) for 3 days or intramuscularly (50 mg/kg), also for 3 days, and the residues were determined by liquid chromatography in albumen and yolk. The sensitivity of the whole procedure was 2 ng/g. The drug was excreted preferentially into the yolk (about 57% of the total) and the elimination period lasted for 4-6 days after treatment.

The safety of dimetridazole alone and in conjunction with oxytetracycline in Hereford crossbred steers.

Dimetridazole was given intraruminally alone, and in conjunction with oxytetracycline to healthy, 10-11 month-old Hereford cross-bred steers (n = 6). Intraruminal treatment with dimetridazole was given through a fistula at 75 mg kg-1 daily for 5 d, while the oxytetracycline was injected intramuscularly at 10 mg kg-1 on Days 1 and 3 of the dimetridazole treatment. The animals were observed at various intervals throughout the trial period for adverse reactions, including effects on ruminal activity and motility, changes in live-mass, venous acid-base balance, haematology and ruminal and serum ammonia concentrations. Dimetridazole, either when used alone or in conjunction with oxytetracycline, had a marked effect on ruminal function. Within 6 h of dosing, the ruminal pH fell to below 5, but then returned to pretreatment values over the next 24-48 h. This was followed by the eradication of the ruminal protozoal population in all animals tested and an increase in the methylene blue reduction time to more than 6 min. Ruminal motility remained unaffected throughout this period. During the week of treatment, the mean live-mass of the animals dropped by 20 +/- 9.9 kg in the dimetridazole treated group and by 13.3 +/- 2.8 kg in the animals treated with both dimetridazole and oxytetracycline. A mild to severe watery diarrhoea, which continued for 1 to 2 d, occurred in 4 animals after the first dimetridazole treatment. A compensated metabolic acidosis and an increase in haematocrit were observed. An initial transient rapid rise in rumen ammonia concentrations did not result in a concurrent rise in serum ammonia concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

The use of metronidazole, tinidazole and dimetridazole in eliminating trichomonads from laboratory mice.

Metronidazole, tinidazole and dimetridazole were administered in the drinking water for 5 days to mice experimentally infected with Tritrichomonas muris and Tetratrichomonas microta. Mice were successfully infected with T. muris and T. microta recovered from infected gerbils. The trichomonas infection was successfully eliminated in mice given a 1% sucrose solution containing 2.5 mg/ml metronidazole or tinidazole. Mice receiving 1.0 mg/ml metronidazole, 1.0 mg/ml tinidazole and 1.2, 5.0 and 10.0 mg/ml dimetridazole failed to eliminate the trichomonas organism. A reduction in water intake was only noted with mice receiving 10 mg/ml dimetridazole. In mice receiving only 1% sucrose the infection was not eliminated.

Toxicity of dimetridazole in waterfowl.

Dimetridazole at a concentration of 1.0 g/l in drinking water caused mortality in both ducklings and goslings. When given to goslings at a concentration of 0.5 g/l, the drug caused growth depression and nervous signs characterized by excess activity, abnormal head attitudes, and ataxia.

[Prophylactic use of drugs in sows in industrial swine breeding]. / Medikamentozna profilaktika pri svinete-maiki v usloviiata na promishlenoto svinevudstvo.

Four scientific-and-economic experiments were carried out with 4 groups of sows each, the animals being equated in terms of age and period of farrowing (+/- 4 days). Both test and control groups were offered rations of one and the same composition and amount. The feed of the test groups contained medicated premixes MNDm (neomycin and dimetridazol) or MODm (oxatetracyclin and dimetridazol) at the rate of 1 per cent. The medicated feed was fed to the sows 3 days prior to and 7 days after farrowing. At the time of weaning newborn pigs were given combined feed in the course of 5-6 days with the inclusion of medicated premixe MOSdf (oxatetracyclin, sulfadimezin, and furazolidan) also at the rate of 1 per cent. A total of 1774 pigs were obtained from all 182 test sows at an average fertility rate of 9.8 pigs per sow. The control of 182 cows yielded 1747 pigs (fertility rate of 9.7). The average weight gain of the test pigs during the suckling period amounted to 212 g against 197 g for the controls (an increase of 15 g -- 7.6 per cent). Mortality ranged from 78 pigs for the test groups to 101 pigs for the control ones. Up to 7 cases of diseased sows were established with the test animals against 24 ones with the controls. The number of impregnated sows up to the 20th day after weaning the newborns was 90 for the test animals against 77 for the control ones, and the number of returns was 27 and 34, respectively. Owing to sterility 5 sows of the test groups and 11 sows of the control groups were culled (4.2 vs. 9.0 per cent). Conclusions were drawn that the medicated premixes MNDm and MODm, used in amounts of 1 per cent with the combined feed prevented endometritis, mastitis, agalaxia, enteritis, and other diseases in sows. The treated animals exhibited joint estrus by groups after weaning the newborns, manifesting a higher conception rate. Parallel to this, the weight development of newborn pigs was improved, and mortality during the sucking period was reduced.